Endocrinology 5 - Hyperthyroid disorders Flashcards
List the classes of drugs used in treatment of hyperthyroidism
- Thionamides (thiourylenes; anti-thyroid drugs eg. peopylthiouracil [PTU] and carbimazole)
- Potassium iodide
- Radioiodine
- B-blockers
- First 3 reduce thyroid hormone synthesis, while beta-blockers don’t affect synthesis but help to manage the symptoms
List the uses of thionamides
- Daily treatment of hyperthyroid conditions (Graves/ toxic thyroid nodule)
- Treatment prior to surgery
- Reduction of symptoms while waiting for radioactive iodine to act
Briefly summarise thyroid hormone synthesis
- Uptake of iodide by active transport
- Iodination
- Coupling reaction (storage in colloid) makes T3/T4
- Endocytosis
Describe the mechanism of action of thionamides
- Inhibition of thyroid peroxidase and hence T3/4 synthesis and secretion
- May suppress antibody production in Graves disease
- Reduces conversion of T4 to T3 in peripheral tissues
List the unwanted actions of thionamides
- Agranulocytosis (reduction in neurophils) - rare and reversible
- Rashes
Describe the pharmacokinetics of thionamides
- Orally active
- Carbimazole is a pro-drug which first has to be converted to metimazole
- Cross placenta, secreted in breastmilk (carbimazole more than PTU)
- Metabolised in the liver and excreted in urine
What is the follow up procedure in patients on thionamides?
- Usually aim to stop anti-thyroid drug treatment after 18 months
- Review periodically including thyroid function tests for remission/relapse
How are beta blockers used in thyrotoxicosis treatment?
- Several weeks for ATDs to have clinical effects (reduced tremor, slower heart rate and less anxiety)
- Non-selective beta blockers like propanolol achieve these effects in the meantime
When are (potassium) iodides used in thyrotoxicosis treatment?
- Preparation of hyperthyroid patients for surgery
- Severe thyrotoxic crisis (thyroid storm) - they allow you to act quickly
List the unwanted actions of potassium iodide?
Allergic reactions (rashes, fever and angiooedema)
Describe the parmacokinetics of potassium iodide
- Given orally (lugols solution or aqueous iodine)
- Maximum effects after 10 days continuous administration
List the uses of radioiodine and its mechanism
- Treats hyperthyroidism (graves/toxic nodular disease) and thyroid cancers.
- Before pregnancy this would work so the patient wouldn’t need to take any anti-thyroid drugs
- Accumulates in colloid and emits beta particles, destroying follicular cells
Describe the pharmacokinetics of radioiodine
- Discontinue anti-thyroid drugs 7-10 days prior to radioiodine treatment
- Administered as a single oral dose
- Radioactive half life of 8 days
- Radioactivity negligible after 2 months
List the cautions of radioiodine treatment
- Avoid close contact with small children for several weeks after receiving radioiodine
- Contra-indicated in pregnancy (wait 6 months) and breast feeding
What causes hyperthyroidism?
- Graves disease (autoimmune)
- Nodular goitre (plummers disease)
List the characteristics of graves disease?
- Antibodies stimulate TSH receptor
- Cause a smooth goitre and hyperthyroidism
List the features of hyperthyroidism
- Diarrhoea
- Nervousness
- Tachycardia
- Palpatations
- Loss of weight
- Very hungry
- Tremour
- Muscle weakness
- Localised pretibial myxoedema (no pits form when pressed)
- Graves opthalmopathy and exopthalmos (big staring eyes)
- Lid lag
- Breathlessness
- Causes the eyes to bulge and shins to swell (three different antibodies cause each)
What is plummers disease caused by?
- A benign tumour of the thyroid fland
- Not autoimmune, no pretibial myxoedema, no smoothly enlarged goitre - it is nodular (one part of the thyroid gland grows - hot nodule).
- As one part of the thyroid gland is producing lots of thyroxine, the rest of the thyroid gland begins to shrink
List the effects of thyroxine on the SNS
- Sensitises beta-adrenoreceptors to ambient levels of adrenaline and noradrenaline
- There is apparent sympathetic stimulation
- This results in tachycardia, palpitations, tremour in hands and lid lag
How is hyperthyroidism identified (not including blood test)?
- Test for lid lag (lids close just after eyes go down, so you can see whites of their eyes at the top)
- Ask the patient to swallow water and feel the thyroif gland for goitre
What is a thyroid storm?
- Patient has very very high thyroxine levels
- 50% mortality when untreated
List the features of thyroid storm.
- Cardiac failure
- Delirium/ frank psychosis
- Hepatocellular dysfunction (jaundice)
- Hyperpyrexia (>41 degrees)
- Arrythmia/tachycardia
How can thyroid storm be treated?
- Surgery (thyroidectomy)
- Radioiodine
- Drugs
How quickly do thionamides work?
- Biochemically it takes hours
- Clinical effect takes weeks, so the symptoms are not improving
How does potassium iodide work in thyrotoxicosis treatment?
- Large doses of iodide inhibits iodination of thyroglobulin, hydrogen peroxide generation and thyroperoxidase. Walff-chaikoff effect (autoregulatory)
- Symptoms reduce within 1-2 days
- Size of gland and vascularity reduce within 10-14 days
How can you distinguish between graves disease and thyroiditis?
In thyroiditis the goitre will be tender to the touch, it is not in graves.
List the signs of graves disease that would be observed in the eyes
- Bilateral exophthalmos (bulging eyes)
- Lid lag
- Staring eyes
- Can see the whites of the eyes around the iris
What do you need to be wary of in surgery on the thyroid gland?
- Recurrent laryngeal nerve (can result in deep voice)
- Parathyroid gland
